NM_007283.7:c.262+26091C>T

Variant names:

• chr3-127755698-G-A
• rs17282181
• NM_007283.7:c.262+26091C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007283.7(MGLL):​c.262+26091C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 152,102 control chromosomes in the GnomAD database, including 3,764 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.20 (3764 hom., cov: 32)
• Consequence: MGLL NM_007283.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.609
• Publications: 6 publications found

Genes affected

MGLL (HGNC:17038): (monoglyceride lipase) This gene encodes a serine hydrolase of the AB hydrolase superfamily that catalyzes the conversion of monoacylglycerides to free fatty acids and glycerol. The encoded protein plays a critical role in several physiological processes including pain and nociperception through hydrolysis of the endocannabinoid 2-arachidonoylglycerol. Expression of this gene may play a role in cancer tumorigenesis and metastasis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Feb 2012]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MGLL	NM_007283.7	c.262+26091C>T		intron_variant	Intron 3 of 7	ENST00000265052.10	NP_009214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MGLL	ENST00000265052.10	c.262+26091C>T		intron_variant	Intron 3 of 7	1	NM_007283.7	ENSP00000265052.5

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30328 AN: 151984 Hom.: 3755 Cov.: 32

Gnomad AFR AF: 0.0586

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.188

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.199 AC: 30342 AN: 152102 Hom.: 3764 Cov.: 32 AF XY: 0.204 AC XY: 15148 AN XY: 74346

African (AFR) AF: 0.0585 AC: 2427 AN: 41504

American (AMR) AF: 0.266 AC: 4059 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 1094 AN: 3464

East Asian (EAS) AF: 0.167 AC: 867 AN: 5186

South Asian (SAS) AF: 0.269 AC: 1292 AN: 4808

European-Finnish (FIN) AF: 0.277 AC: 2928 AN: 10564

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.249 AC: 16954 AN: 67974

Other (OTH) AF: 0.188 AC: 398 AN: 2116

Alfa AF: 0.238 Hom.: 9409

Bravo AF: 0.189

Asia WGS AF: 0.217 AC: 754 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.78
DANN	Benign	0.77
PhyloP100		-0.61
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17282181; hg19: chr3-127474541;